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To investigate the quantitative impact of fatigue on health-related quality of life (HRQoL) in multiple sclerosis (MS) and to determine whether fatigue was related to HRQoL independently from bodily disability, data on HRQoL were ascertained for 87 patients with definite MS by using the SF-36. HRQoL scores and subscores were related to the basic MS disability score (EDSS) and further MS parameters, and to fatigue, which was assessed by using different fatigue scales. Factors related to predominantly physical but not mental HRQoL aspects were identified as related to EDSS, duration of disease, and age. Different fatigue scores did impact significantly on both physical and especially mental HRQoL. The influence of fatigue on physical HRQoL was independent from EDSS. Fatigue experience reduces HRQoL markedly and independently from EDSS. Therefore, fatigue assessment provides additional information to disability-derived scales such as the EDSS with relevant implications for therapeutic decisions.

BackgroundAs a multi-targeted anti-angiogenic receptor tyrosine kinase (RTK) inhibitor sunitinib (SUN) has been established for renal cancer and gastrointestinal stromal tumors. In advanced refractory esophagogastric cancer patients, monotherapy with SUN was associated with good tolerability but limited tumor response.MethodsThis double-blind, placebo-controlled, multicenter, phase II clinical trial was conducted to evaluate the efficacy, safety and tolerability of SUN as an adjunct to second and third-line FOLFIRI (NCT01020630). Patients were randomized to receive 6-week cycles including FOLFIRI plus sodium folinate (Na-FOLFIRI) once every two weeks and SUN or placebo (PL) continuously for four weeks followed by a 2-week rest period. The primary study endpoint was progression-free survival (PFS). Preplanned serum analyses of VEGF-A, VEGF-D, VEGFR2 and SDF-1α were performed retrospectively.ResultsOverall, 91 patients were randomized, 45 in each group (one patient withdrew). The main grade ≥3 AEs were neutropenia and leucopenia, observed in 56 %/20 % and 27 %/16 % for FOLFIRI + SUN/FOLFIRI + PL, respectively. Median PFS was similar, 3.5 vs. 3.3 months (hazard ratio (HR) 1.11, 95 % CI 0.70–1.74, P = 0.66) for FOLFIRI + SUN vs. FOLFIRI + PL, respectively. For FOLFIRI + SUN, a trend towards longer median overall survival (OS) compared with placebo was observed (10.4 vs. 8.9 months, HR 0.82, 95 % CI 0.50–1.34, one-sided P = 0.21). In subgroup serum analyses, significant changes in VEGF-A (P = 0.017), VEGFR2 (P = 0.012) and VEGF-D (P < 0.001) serum levels were observed.ConclusionsAlthough sunitinib combined with FOLFIRI did not improve PFS and response in chemotherapy-resistant gastric cancer, a trend towards better OS was observed. Further biomarker-driven studies with other anti-angiogenic RTK inhibitors are warranted.Trial registrationThis study was registered prospectively in the NCT Clinical Trials Registry (ClinicalTrials.gov) under NCT01020630 on November 23, 2009 after approval by the leading ethics committee of the Medical Association of Rhineland-Palatinate, Mainz, in coordination with the participating ethics committees (see Additional file 2) on September 16, 2009.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2736-9) contains supplementary material, which is available to authorized users.

Aims In a randomized, parallel, blinded study, we investigate the impact of clopidogrel, prasugrel, or ticagrelor on peripheral endothelial function in patients undergoing stenting for an acute coronary syndrome. Methods and results The primary endpoint of the study was the change in endothelium-dependent flow-mediated dilation (FMD) following stenting. A total of 90 patients (age 62 ± 9 years, 81 males, 22 diabetics, 49 non-ST elevation myocardial infarctions) were enrolled. There were no significant differences among groups in any clinical parameter. Acutely before stenting, all three drugs improved FMD without differences between groups (P = 0.73). Stenting blunted FMD in the clopidogrel and ticagrelor group (both P &lt; 0.01), but not in the prasugrel group. During follow-up, prasugrel was superior to clopidogrel [mean difference 2.13, 95% confidence interval (CI) 0.68–3.58; P = 0.0047] and ticagrelor (mean difference 1.57, 95% CI 0.31–2.83; P = 0.0155), but this difference was limited to patients who received the study therapy 2 h before stenting. Ticagrelor was not significantly superior to clopidogrel (mean difference 0.55, 95% CI −0.73 to 1.82; P = 0.39). No significant differences were seen among groups for low-flow-mediated dilation. Plasma interleukin (IL)-6 (P = 0.02 and P = 0.01, respectively) and platelet aggregation reactivity in response to adenosine diphosphate (P = 0.002 and P = 0.035) were lower in the prasugrel compared to clopidogrel and ticagrelor group. Conclusion As compared to ticagrelor and clopidogrel, therapy with prasugrel in patients undergoing stenting for an acute coronary syndrome is associated with improved endothelial function, stronger platelet inhibition, and reduced IL-6 levels, all of which may have prognostic implications. This effect was lost in patients who received the study medication immediately after stenting. EUDRACT-No 2011-005305-73

We investigate sleep and breathing in clinically stable myasthenia gravis (MG) patients and ask weather sleep disordered breathing (SDB) is causally linked with MG. Nineteen MG patients with a mean disease duration of 9.7 years underwent sleep studies in two consecutive nights. The primary outcome measure was the respiratory disturbance index (RDI) in terms of snoring and apneas/hypopneas. Further outcome measurements were total sleep time, sleep stage distribution and the number of arousals. A clinically relevant SDB in terms of obstructive sleep apnea (OSA) (defined as RDI > 10/h) was found in four patients. There were only a few central apneas (central apnea index: 0.19 +/- 0.4/h). We did not find a relationship between maximum inspiratory pressure and SDB (r = -0.03). There is no evidence for a causal relationship between medically stable MG and SDB in terms of OSA. The extent of respiratory muscle weakness failed to correlate with SDB. Furthermore, our study does not confirm the high occurrence of central respiratory events during sleep in patients with well-controlled MG.

Aims/hypothesis Individuals with type 2 diabetes mellitus may experience an asymptomatic period of hyperglycaemia, and complications may already be present at the time of diagnosis. We aimed to determine the prevalence of diabetic retinopathy in patients with newly diagnosed (screeningdetected) type 2 diabetes. Methods The Gutenberg Health Study is a population-based study with 15,010 participants aged between 35 and 74 years. We determined the weighted prevalence of diabetic retinopathy by assessing fundus photographs. Screeningdetected type 2 diabetes was defined as an HbA 1c concentration of 6.5% (47.5 mmol/mol) or more, no medical diagnosis of diabetes and no intake of insulin or oral glucoselowering agents. Results Of 14,948 participants, 1377 (9.2%) had diabetes mellitus. Of these, 347 (25.2%) had newly diagnosed type 2 diabetes detected by the screening. Overall, the weighted prevalence of screening-detected type 2 diabetes was 2.1%. Fundus photos were evaluable for 285 (82.1%) participants with newly diagnosed diabetes. The weighted prevalence of diabetic retinopathy in screening-detected type 2 diabetes was 13.0%; 12% of participants had a mild non-proliferative diabetic retinopathy and 0.6% had a moderate nonproliferative diabetic retinopathy. Diabetic retinopathy was proliferative in 0.3%. No cases of severe non-proliferative diabetic retinopathy or diabetic maculopathy were found. Thirty (14.9%) of 202 and six (7.2%) of 83 individuals with and without concomitant arterial hypertension, respectively, had diabetic retinopathy (OR 2.54, 95% CI 1.06, 7.14). Visual acuity did not differ between individuals with and without diabetic retinopathy . Conclusions/interpretation In this large European study, the prevalence of diabetic retinopathy in screening-detected type 2 diabetes was 13%. Only a very small proportion of participants with detected diabetic retinopathy needed treatment.